Determinants of thoracic aortic size in normotensive and hypertensive individuals.

AIMS: Thoracic aortic diameter is modulated by various factors including both physiological and pathological mechanisms. The aim of this study was to explore the determinants of thoracic aortic size focusing on arterial blood pressure and physical activity in normotensive and hypertensive individuals. METHODS: Ascending and descending aortic diameters were measured in participants of the Copenhagen General Population Study using thoracic CT angiography. To assess the relation between arterial blood pressure and thoracic aortic diameters, individuals with diabetes, hypercholesterolemia, smoking, and prescribed antihypertensive medication were excluded. Intensity of physical activity was recorded based on self-reported questionnaire data. RESULTS: A total of 1214 normotensive and 284 hypertensive individuals were examined. In all individuals, male sex, older age, and body surface area were associated with higher diameters of the ascending and descending aorta (P < 0.01). In normotensive individuals, hard physical activity > 4 h/week was independently associated with higher thoracic aortic diameters (ascending ß:1.09[0.52;1.66] and descending ß: 0.47[0.14;0.80], both P < 0.01), whereas higher systolic blood pressure was not associated with thoracic aortic diameters (ascending P = 0.12 and descending p = 0.33). In hypertensive individuals, higher systolic blood pressure (per 10 mmHg) was independently associated with higher thoracic aortic diameters (ascending ß: 0.55[0.17;0.94] and descending ß: 0.23[0.10;0.37] mm/10 mmHg, both P < 0.01), whereas hard physical activity was not associated with higher aortic diameters (ascending P = 0.11 and descending P = 0.51). CONCLUSION: In normotensive individuals hard physical activity, and in hypertensive individuals increasing systolic blood pressure are factors each independently associated with larger thoracic aortic size. These findings suggest a context sensitive mode of aortic vascular response to size modulating adaptation.

Comparative Rates of Stroke and Rehospitalization of Atrial Fibrillation in Patients with Perioperative Atrial Fibrillation Following Major Emergency Abdominal Surgery and Patients with Non-perioperative Atrial Fibrillation.

BACKGROUND: Major emergency abdominal surgery is associated with postoperative complications and high mortality. Long-term outcomes in patients with perioperative atrial fibrillation (POAF) have recently received increased attention, especially POAF in non-thoracic surgery. PURPOSE: This study aimed to compare long-term AF related hospitalization and stroke in patients with POAF in relation to major emergency abdominal surgery and in patients with non-perioperative AF. METHODS: We crosslinked data from Danish nationwide registries and identified all patients who underwent major emergency abdominal surgery (2000-2018) and were diagnosed with POAF, and patients who developed AF in a non-perioperative setting. Patients with POAF were matched in a 1:5 ratio on age, sex, year of AF diagnosis and oral anticoagulation (OAC) status at the beginning of follow-up with patients with non-perioperative AF. From discharge, we examined adjusted hazard ratios (HR) of stroke using multivariable Cox regression analysis. RESULTS: The study population comprised 1,041 (out of 42,021 who underwent major emergency abdominal surgery) patients with POAF and 5,205 patients with non-perioperative AF. The median age was 78 years [interquartile range: 71-84] for those initiated on OAC therapy and 78 years [interquartile range: 71-85] for those not initiated on OAC therapy. During the first year of follow up, POAF was associated with similar rates of stroke as non-perioperative AF (patients initiated on OAC: HR 0.96 (95% confidence interval (CI) 0.52-1.77) and patients not initiated on OAC: HR 0.69 (95% CI 0.41-1.15). CONCLUSION: POAF in relation to major emergency abdominal surgery was associated with similar rates of stroke as non-perioperative AF. These results suggest that POAF not only carry an acute burden but also a long-term burden in patients undergoing major emergency abdominal surgery.

Early surgery to prevent embolic events in patients with infective endocarditis: a comprehensive review.

BACKGROUND: Infective endocarditis (IE) is a dangerous and lethal illness with high mortality rates. One of the main indications for surgery according to the guidelines is prevention of embolic events. However, uncertainty remains concerning the timing of surgery and the effect of early surgery in combination with antibiotic therapy versus antibiotic therapy alone in IE patients with a vegetation size > 10 mm. METHODS: We conducted a comprehensive review by searching the PubMed, MEDLINE, and EMbase databases. Titles and abstracts were screened, and studies of interest were selected for full-text assessment. Studies were selected for review if they met the criteria of comparing surgical treatment + antibiotic therapy to antibiotic therapy alone in patients with vegetations > 10 mm. RESULTS: We found 1,503 studies through our database search; nine of these were eligible for review, with a total number of 3,565 patients. Median age was 66 years (range: 17-80) and the median percentage of male patients was 65.6% (range: 61.8 - 71.4%). There was one randomised controlled trial, one prospective study, and seven retrospective studies. Seven studies found surgery + antibiotic therapy to be associated with better outcomes in patients with IE and vegetations > 10 mm, one of them being the randomised trial [hazard ratio = 0.10; 95% confidence interval 0.01-0.82]. Two studies found surgery + antibiotic therapy was associated with poorer outcomes compared with antibiotic therapy alone. CONCLUSION: Overall, data vary in quality due to low numbers and selection bias. Evidence is conflicting, yet suggest that surgery + antibiotic therapy is associated with better outcomes in patients with IE and vegetations > 10 mm for prevention of emboli. Properly powered randomised trials are warranted.

Incidence of clinical outcomes in heart failure patients with and without advanced chronic kidney disease.

AIMS: Chronic kidney disease (CKD) is a well-established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 have been systematically excluded from clinical trials. This study investigated the incidence of HF and kidney outcomes in HF patients with and without advanced CKD, that is, eGFR < 30. METHODS: From nationwide registries, HF patients were identified from 2014 to 2018 and categorized into three groups according to baseline eGFR (eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30). The incidence of primary outcomes (all-cause mortality, HF hospitalization, end-stage kidney disease and sustained 50% eGFR decline) was estimated using cumulative incidence functions. RESULTS: Of the 21 959 HF patients included, the median age was 73.9 years, and 30% of patients had an eGFR between 30 and 60 and 7% had an eGFR < 30. The 4 year incidence of all-cause mortality was highest for patients with eGFR < 30 (28.3% for patients with eGFR ≥ 60, 51.6% for patients with 60 > eGFR ≥ 30 and 72.2% for patients with eGFR < 30). The 4 year incidence of HF hospitalization was comparable between the groups (25.8%, 29.8% and 26.1% for patients with eGFR ≥ 60, 60 > eGFR ≥ 30 and eGFR < 30, respectively). For patients with eGFR < 30, kidney outcomes were four times more often the first event than patients with eGFR > 30 (4 year incidence of kidney outcome as the first event was 5.0% for eGFR ≥ 60, 4.8% for 60 > eGFR ≥ 30 and 20.1% for eGFR < 30). CONCLUSIONS: Patients with advanced CKD had a higher incidence of mortality and poorer kidney outcomes than those without advanced CKD, but a similar incidence of HF hospitalizations.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

BACKGROUND: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. METHODS: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. RESULTS: Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). CONCLUSIONS: In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Aortic dimensions in women with previous pre-eclampsia.

BACKGROUND: Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of aortic dilatation and aneurysm development. It is, however, unknown if younger women with previous pre-eclampsia have increased aortic dimensions. We tested the hypothesis that previous pre-eclampsia is associated with increased aortic dimensions in younger women. METHODS: The study was a cross-sectional cohort study of women with previous pre-eclampsia, aged 40-55, from the PRECIOUS population matched by age and parity with women from the general population. Using contrast-enhanced CT, aortic diameters were measured in the aortic root, ascending aorta, descending aorta, at the level of the diaphragm, suprarenal aorta, and infrarenal aorta. RESULTS: 1355 women (684 with previous pre-eclampsia and 671 from the general population), with a mean (standard deviation) age of 46.9 (4.4) were included. The pre-eclampsia group had larger mean (standard deviation) aortic diameters (mm) in all measured segments from the ascending to the infrarenal aorta (ascending: 33.4 (4.0) vs. 31.4 (3.7), descending: 23.9 (2.1) vs. 23.3 (2.0), diaphragm: 20.8 (1.8) vs. 20.4 (1.8), suprarenal: 22.9 (1.9) vs. 22.0 (2.0), infrarenal: 19.3 (1.6) vs. 18.6 (1.7), p â€‹< â€‹0.001 for all, also after adjustment for age, height, parity, menopause, dyslipidemia, smoking and chronic hypertension. Guideline-defined ascending aortic aneurysms were found in 8 vs 2 women (p â€‹= â€‹0.12). CONCLUSIONS: Women with previous pre-eclampsia have larger aortic dimensions compared with women from the general population. Pre-eclampsia was found to be an independent risk factor associated with a larger aortic diameter.

Association Between Vegetation Size and Outcome in the Partial Oral Antibiotic Endocarditis Treatment Trial.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

Surgery in patients with infective endocarditis and prognostic importance of patient frailty.

PURPOSE: Surgery is required in 20-50% of patients with infective endocarditis (IE). Frailty increases surgical risk; however, the prognostic implications of frailty in patients undergoing IE-related surgery remain poorly understood. We aimed to assess the association between frailty and all-cause mortality or rehospitalization after discharge (≥ 14 days). METHODS: We identified all IE patients who underwent surgery during admission (2010-2020) in Denmark. The Hospital Frailty Risk Score was used to categorize patients into two frailty risk groups, patients with low frailty scores (< 5 points) and frail patients (≥ 5 points). We analyzed time hospitalized after discharge and all-cause mortality from the date of surgery with a one-year follow-up. Statistical analyses utilized the Kaplan-Meier estimator, Aalen-Johansen estimator, and the Cox regression model. RESULTS: We identified 1282 patients who underwent surgery during admission, of whom 967 (75.4%) had low frailty scores, and 315 (24.6%) were frail. Frail patients were characterized by advanced age, a lower proportion of males, and a higher burden of comorbidities. Frail patients were more hospitalized (> 14 days) in the first post-discharge year (19.1% vs.12.3%) compared to patients with low frailty scores. Additionally, frail patients had higher rates of all-cause mortality including in-hospital deaths (27% vs. 15%) and rehospitalizations (43.5% vs 26.1%) compared to patients with low frailty scores. This was also evident in the adjusted analysis (hazard ratio 1.36 [CI 95% 1.09-1.71]). CONCLUSION: Frailty was associated with an ≈40% increased rate of rehospitalization (≥ 14 days) or death. Further studies are needed to assess the effectiveness of surgery with a focus on frailty to improve prognostic outcomes in these patients.

Mortality and Heart Failure Admission After Mitral Valve Surgery for Mitral Regurgitation in Patients With Versus Without a History of Atrial Fibrillation: A Nationwide Study.

This study aimed to examine the associated rate of 3-year mortality and heart failure (HF) admission in patients who underwent mitral valve replacement/repair (MVR) for mitral regurgitation (MR) with and without a history of atrial fibrillation (AF). Using Danish nationwide registries, we categorized adult patients who underwent MVR for MR from 2000 to 2018 according to history of AF. The cumulative incidence of all-cause mortality and HF admission with a maximum of 3 years of follow-up were examined using Kaplan-Meier and the Aalen Johansen estimator, respectively. The adjusted rates were computed using the multivariable Cox regression analysis. We included 4,480 patients: 1,685 with a history of AF (37.6%) (median age 70 years, 66.1% men) and 2,795 (without AF 62.4%) (median age 64 years, 67.6% men). The 3-year mortality was 13.8% for patients with AF and 8.2% for patients without AF. The adjusted analysis yielded no statistically significant difference in the associated rate of mortality between the study groups (hazard ratio 1.16, 95% confidence interval 0.95 to 1.43, reference: no AF). The cumulative 3-year incidence of HF admission was 23.7% for patients with AF and 14.6% for patients without AF. The adjusted analysis yielded an associated higher rate of HF admission for patients with a history of AF (hazard ratio 1.19, 95% confidence interval 1.02 to 1.39). In conclusion, 37.6% of patients who underwent MVR for MR had a history of AF before surgery and we found no statistically significant difference in the mortality between the study groups but found a higher associated rate of HF admission in patients with a history of AF.

Aortic aneurysms in a general population cohort: prevalence and risk factors in men and women.

BACKGROUND AND AIMS: The prevalence and difference in risk factors for having thoracic and abdominal aortic aneurysms in men compared to women in the general population is not well-described. This study aimed to test the hypotheses i) that cardiovascular risk factors for thoracic and abdominal aortic aneurysms differ and ii) that the prevalence of thoracic and abdominal aortic aneurysms is sex specific. METHODS: Aortic examination using computed tomography angiography was performed in 11,294 individuals (56% women), with a mean age of 62 [range 40-95] years participating in the Copenhagen General Population Study. Thoracic aortic aneurysms were defined as ascending aortic diameter ≥45 mm and descending aortic diameter ≥35 mm, abdominal aortic aneurysms were defined as abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. RESULTS: Overall prevalence of aortic aneurysms in the study population included: total population 2.1%, men 4.0% and women 0.7% (p-test men vs. women p<0.001). Aortic aneurysms were independently associated with male sex, increasing age, and body surface area. While thoracic aortic aneurysms were associated with hypertension, odds ratio=2.0[95%CI:1.5-2.8], abdominal aortic aneurysms were associated with hypercholesterolemia and smoking, odds ratios=2.4[95%CI:1.6-3.6] and 3.2[95%CI:1.9-5.4]. CONCLUSIONS: Subclinical aortic aneurysms are four times more prevalent in men than women. In both sexes, increasing age and body surface area are risk factors for aortic aneurysms of any anatomical location. Whereas arterial hypertension is a risk factor for thoracic aortic aneurysms, hypercholesterolemia and smoking are risk factors for abdominal aortic aneurysms.

Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI.

BACKGROUND: Patients who sustain an acute myocardial infarction (AMI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remain at high risk for heart failure (HF), coronary events, and death. Angiotensin-converting enzyme inhibitors have been shown to significantly decrease the risk for cardiovascular events in both STEMI and NSTEMI patients. OBJECTIVES: The objectives were to determine whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan, compared with ramipril, has impact on reducing cardiovascular events according to the type of AMI. METHODS: The PARADISE-MI (Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial enrolled patients with AMI complicated by left ventricular dysfunction and/or pulmonary congestion and at least 1 risk-enhancing factor. Patients were randomized to either sacubitril/valsartan or ramipril. The primary endpoint was death from cardiovascular causes or incident HF. In this prespecified analysis, we stratified patients according to AMI type. RESULTS: Of 5,661 enrolled patients, 4,291 (75.8%) had STEMI. These patients were younger and had fewer comorbidities and cardiovascular risk factors than NSTEMI patients. After adjustment for potential confounders, the risk for the primary outcome was marginally higher in NSTEMI vs STEMI patients (adjusted HR: 1.19; 95% CI: 1.00-1.41), with borderline statistical significance (P = 0.05). The primary composite outcome occurred at similar rates in patients randomized to sacubitril/valsartan vs ramipril in STEMI (10% vs 12%; HR: 0.87; 95% CI: 0.73-1.04; P = 0.13) and NSTEMI patients (17% vs 17%; HR: 0.97; 95% CI: 0.75-1.25; P = 0.80; P interaction = 0.53). CONCLUSIONS: Compared with ramipril, sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI. (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI; NCT02924727).

Normal values of myocardial blood flow measured with dynamic myocardial computed tomography perfusion.

AIMS: Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. CONCLUSION: MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP.

Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV.

BACKGROUND: The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. METHODS: Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). RESULTS: Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048). CONCLUSIONS: PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.

Long-Term Risk of VTE in Sarcoidosis: A Nationwide Cohort Study.

BACKGROUND: Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse. RESEARCH QUESTION: Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population? STUDY DESIGN AND METHODS: Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE. RESULTS: We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15). INTERPRETATION: In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.

Sex differences in infective endocarditis: a Danish nationwide study.

PURPOSE: Sex differences in infective endocarditis (IE) are reported, but patient characteristics are sparse and conflicting findings on the association between sex and short-term outcomes demand further research. We aimed to characterize sex differences in IE in terms of patient characteristics, frailty, microbiology, socioeconomic status, management and outcome on a nationwide scale. METHODS: Between 2010 and 2020, we used Danish national registries to characterize patients with IE according to sex using ICD codes and microbiological lab reports. Frailty was assessed with the Hospital Frailty Risk Score. Mortality was reported with Kaplan-Meier estimates. Logistic regression and Cox regression were used for adjusted analyses. RESULTS: We included 6259 patients with IE with 2047 (32.7%) female patients and 4212 (67.3%) male patients. Female patients were older (median age 75.0 years (64.3-82.2) vs. 71.7 (61.7-78.9)) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%). Staphylococcus aureus-IE were most common in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus-IE (10.5% vs. 18.1%). Female patients were less surgically treated (14.0% vs. 21.2%). Female sex was associated with increased in-hospital mortality (adj. OR 1.33, 95% CI 1.16-1.52), but no statistically significant difference in associated 1- and 5-year mortality from hospital discharge were identified (adj. HR 1.09, 95% CI 0.95-1.24 and 1.02, 95% CI 0.92-1.12, respectively). CONCLUSION: Female sex is associated with increased in-hospital mortality, but not in long-term mortality as compared with male patients. Female patients have a lower prevalence of Enterococcus-IE and rates of surgery. Further research is needed to understand these differences.

Clonal hematopoiesis of indeterminate potential in persons with HIV.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons with HIV (PWH). METHODS: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 50% stenosis. RESULTS: In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A , TET2 , and ASXL1 , accounting for 49, 25, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1ß, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP, and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses. CONCLUSION: In older, well treated, Scandinavian PWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.

Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020.

Microbiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen-Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan-Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, "other microbiological etiologies", and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.

Perioperative Atrial Fibrillation and One-year Clinical Outcomes in Patients Following Major Emergency Abdominal Surgery.

The prevalence and impact of perioperative atrial fibrillation (AF) during an admission for major emergency abdominal surgery are sparsely examined. Therefore, this study aimed to compare the 30-day and 1-year outcomes (AF-related hospitalization, stroke, and all-cause mortality) in patients with and without perioperative AF to their major emergency abdominal surgery. All patients without a history of AF who underwent major emergency abdominal surgery from 2000 to 2019 and discharged alive were identified using Danish nationwide registries. Patients with and without perioperative AF (defined as new-onset AF during the index hospitalization) were matched 1:4 on age, gender, year of surgery, and type of surgery. The cumulative incidences and hazard ratios of outcomes were assessed using a multivariable Cox regression analysis comparing patients with and without perioperative AF. A total of 2% of patients were diagnosed with perioperative AF. The matched cohort comprised 792 and 3,168 patients with and without perioperative AF, respectively (median age 78 years [twenty-fifth to seventy-fifth percentile 70 to 83 years]; 43% men). Cumulative incidences of AF-related hospitalizations, stroke, and mortality 1 year after discharge were 30% versus 3.4%, 3.4% versus 2.7%, and 35% versus 22% in patients with and without perioperative AF, respectively. The 30-day outcomes were similarly elevated among patients with perioperative AF. Perioperative AF during an admission for major emergency abdominal surgery was associated with higher 30-day and 1-year rates of AF-related hospitalization and mortality and similar rates of stroke. These findings suggest that perioperative AF is a prognostic marker of increased morbidity and mortality in relation to major emergency abdominal surgery and warrants further investigation.

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

BACKGROUND: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. METHODS: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. FINDINGS: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. INTERPRETATION: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. FUNDING: Department of Cardiology, Herlev and Gentofte University Hospital. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.